Disruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading vision loss. We present here a novel algorithmic approach that generates highly realistic digital models human blood vessels, based on established biophysical principles, fully-connected arterial venous trees with single inlet outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation reconstruction vessel no...

Cancers exhibit spatially heterogeneous, unique vascular architectures across individual samples, cell-lines and patients. This inherently disorganised collection of leaky blood vessels contribute significantly to suboptimal treatment efficacy. Preclinical tools are urgently required which incorporate the inherent variability heterogeneity tumours optimise engineer anti-cancer therapies. In this study, we present a novel computational framework incorporates whole, realistic extracted ex vivo...

Mesoscopic photoacoustic imaging (PAI) enables non-invasive visualisation of tumour vasculature. The visual or semi-quantitative 2D measurements typically applied to mesoscopic PAI data fail capture the 3D vessel network complexity and lack robust ground truths for assessment accuracy. Here, we developed a pipeline quantifying vascular networks captured using tested preservation blood volume structure with topological analysis. Ground truth in silico synthetic vasculatures string phantom...

Abstract The neurovascular mechanisms underpinning the local regulation of cerebral blood flow (CBF) and oxygen transport remain elusive. In this study we have combined novel in vivo imaging cortical microvascular mural cell architecture with mathematical modelling transport, to provide new insights into CBF that would be inaccessible a conventional experimental context. Our indicates vasoconstriction smooth muscle actin-covered vessels, rather than pericyte-covered capillaries, induces...

Abstract Background/Objectives Pseudo-vascular network formation in vitro is considered a key characteristic of vasculogenic mimicry. While many cancer cell lines form pseudo-vascular networks, little known about the spatiotemporal dynamics these formations. Methods Here, we present framework for monitoring and characterising dynamic dissolution networks vitro. The combines time-resolved optical microscopy with open-source image analysis feature extraction statistical modelling. demonstrated...

Accurate measurement of optical absorption coefficients from photoacoustic imaging (PAI) data would enable direct mapping molecular concentrations, providing vital clinical insight. The ill-posed nature the problem coefficient recovery has prohibited PAI achieving this goal in living systems due to domain gap between simulation and experiment. To bridge gap, we introduce a collection experimentally well-characterised phantoms their digital twins. This first-of-a-kind phantom set enables...

Abstract We present a 3D discrete‐continuum model to simulate blood pressure in large microvascular tissues the absence of known capillary network architecture. Our hybrid approach combines 1D Poiseuille flow description for large, discrete arteriolar and venular networks coupled continuum‐based Darcy model, point sources flux, transport bed. evaluate our using vascular imaged from mouse brain medulla/pons multi‐fluorescence high‐resolution episcopic microscopy (MF‐HREM). use fully‐resolved...

In recent years, biological imaging techniques have advanced significantly and it is now possible to digitally reconstruct microvascular network structures in detail, identifying the smallest capillaries at sub-micron resolution generating large 3D structural data sets of size >106 vessel segments. However, this relies on ex vivo imaging; corresponding measures structure flow are limited larger branching vessels not achievable three dimensions for vessels. This suggests use computational...

Mesoscopic photoacoustic imaging (PAI) enables label-free visualization of vascular networks in tissues with high contrast and resolution. Segmenting these from 3D PAI data interpreting their physiological pathological significance is crucial yet challenging due to the time-consuming error-prone nature current methods. Deep learning offers a potential solution; however, supervised analysis frameworks typically require human-annotated ground-truth labels. To address this, an unsupervised...

The subtle relationship between vascular network structure and mass transport is vital to predict improve the efficacy of anticancer treatments. Here, mathematical homogenisation used derive a new multiscale continuum model blood chemotherapy in vasculature interstitium tumour. This framework enables information at range hierarchies be fed into an effective description on length scale behaviour explored through demonstrative case study simplified representation dorsal skinfold chamber,...

3D microscopy of large biological samples (>0.5 cm 3 ) is transforming research. Many existing techniques require trade‐offs between image resolution, sample size, and method complexity. A simple robust instrument with the potential to conduct large‐volume imaging currently exists in form optical high‐resolution episcopic (HREM). However, development date limited single‐fluorescent wavelength nonspecific eosin staining. Herein, developments realize HREM become multifluorescent (MF‐HREM)...

Mycobacterium chimaera ( M. chimaera) is a recently characterised bacterium that can cause life-threatening infections in small numbers of patients who undergo cardiopulmonary bypass during cardiac surgery. The likely mode transmission thought to occur through aerosolisation from contaminated water reservoirs. airborne bacteria then contaminate the surgical field, leading an infection months or even years later. preferred practical solution disrupt these patient remove heater-cooler units...

Photoacoustic mesoscopy visualises vascular architecture at high-resolution up to ~3 mm depth. Despite promise in preclinical and clinical imaging studies, with applications oncology dermatology, the accuracy precision of photoacoustic is not well established. Here, we evaluate a commercial system for structures. Typical artefact types are first highlighted limitations due non-isotropic illumination detection evaluated respect rotation, angularity, depth target. Then, using tailored phantoms...

Abstract Disruption of retinal vasculature is linked to various diseases, including diabetic retinopathy and macular degeneration, leading vision loss. We present here a novel algorithmic approach that generates highly realistic digital models human blood vessels based on established biophysical principles, fully-connected arterial venous trees with single inlet outlet. This approach, using physics-informed generative adversarial networks (PI-GAN), enables the segmentation reconstruction...

Abstract We present a 3D discrete-continuum model to simulate blood pressure in large microvascular tissues the absence of known capillary network architecture. Our hybrid approach combines 1D Poiseuille flow description for large, discrete arteriolar and venular networks coupled continuum-based Darcy model, point sources flux, transport bed. evaluate our using vascular imaged from mouse brain medulla/pons multi-fluorescence high-resolution episcopic microscopy (MF-HREM). use fully-resolved...

Abstract Mesoscopic photoacoustic imaging (PAI) enables label-free visualisation of vascular networks in tissue at high contrast and resolution. The segmentation from 3D PAI data interpretation their meaning the context physiological pathological processes is a crucial but time consuming error-prone task. Deep learning holds potential to solve these problems, current supervised analysis frameworks require human-annotated ground-truth labels. Here, we overcome need for labels by introducing...

Three-dimensional microscopy of large biological samples (>0.5 cm 3 ) is transforming research. Many existing techniques require trade-offs between image resolution, sample size and method complexity. A simple robust instrument with the potential to perform volume 3D imaging currently exists in form Optical HREM, however development date limited single fluorescent wavelength non-specific eosin staining. This work presents developments realize HREM become Multi-fluorescent High Resolution...

Nanoparticles have the potential to increase efficacy of anticancer drugs whilst reducing off-target side effects. However, there remain uncertainties regarding cellular uptake kinetics nanoparticles which could implications for nanoparticle design and delivery. Polymersomes are candidates cancer therapy encapsulate chemotherapy drugs. Here we develop a mathematical model simulate polymersomes via endocytosis, process by bind cell surface before becoming internalised where they then break...

Abstract It is critically important to understand and predict fluid transport within both physiological pathological tissues in order develop effective treatment strategies. Recent advances high-resolution optical imaging allow the acquisition of whole tumour vascular networks which can be used parameterise computational models dynamics at all length scales across tissue. This enables hypothesis testing around role microenvironment determining characteristics, would otherwise unavailable...

Abstract Objective: The formation of functional vasculature in solid tumours enables delivery oxygen and nutrients, is vital for effective treatment with chemotherapeutic agents. Longitudinal characterisation vascular networks can be enabled using mesoscopic photoacoustic imaging, but requires accurate image co-registration to precisely assess local changes across disease development or response therapy. Co-registration imaging challenging due the complex nature generated signal, including...

Abstract Photoacoustic mesoscopy visualises vascular architecture and associated tissue structures at high resolution up to 3 mm depth. The technique has shown promise in both preclinical clinical imaging studies, with possible applications oncology dermatology, however, the accuracy precision of photoacoustic not been well established. Here, we present a performance evaluation commercial system for structures. Typical artefact types are first highlighted limitations due non-isotropic...